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. 1991 Jun;138(6):1405–1411.

Pneumonitis associated with coinfection by human herpesvirus 6 and Legionella in an immunocompetent adult.

S K Russler 1, M A Tapper 1, K K Knox 1, A Liepins 1, D R Carrigan 1
PMCID: PMC1886405  PMID: 1647138

Abstract

The authors report a case of pneumonitis in a young healthy man caused by coinfection with human herpesvirus 6 (HHV-6) and Legionella pneumophila. The patient's course was complicated by severe respiratory, renal, hepatic, and central nervous system dysfunctions, which were believed to be primarily the results of his Legionella infection. Aggressive antibiotic treatment produced no response, and Legionella remained isolatable from lung tissue throughout several weeks of antimicrobial therapy. Human herpesvirus 6 was isolated from a sample of peripheral blood during the acute stage of the patient's illness, and numerous HHV-6--infected macrophages and lymphocytes were detected by immunohistochemical staining of biopsy-derived lung tissue. Paradoxically treatment of the patient with high-dose corticosteroids resulted in dramatic improvement of his condition, including clearance of the Legionella infection. The demonstration that corticosteroids efficiently inhibit HHV-6 replication in vitro suggests that the virus may have contributed to the patient's pneumonitis by enhancing tissue inflammation, by compromising the function of pulmonary macrophages, and, perhaps, by destroying the patient's CD4+ T lymphocytes. Human herpesvirus 6 may be able to function as a synergistic cofactor in lung infections by Legionella and other pathogens.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Asano Y., Yoshikawa T., Suga S., Yazaki T., Hirabayashi S., Ono Y., Tsuzuki K., Oshima S. Human herpesvirus 6 harbouring in kidney. Lancet. 1989 Dec 9;2(8676):1391–1391. doi: 10.1016/s0140-6736(89)91993-4. [DOI] [PubMed] [Google Scholar]
  2. Asano Y., Yoshikawa T., Suga S., Yazaki T., Kondo K., Yamanishi K. Fatal fulminant hepatitis in an infant with human herpesvirus-6 infection. Lancet. 1990 Apr 7;335(8693):862–863. doi: 10.1016/0140-6736(90)90983-c. [DOI] [PubMed] [Google Scholar]
  3. Becker W. B., Engelbrecht S., Becker M. L., Piek C., Robson B. A., Wood L., Jacobs P. Isolation of a new human herpesvirus producing a lytic infection of helper (CD4) T-lymphocytes in peripheral blood lymphocyte cultures--another cause of acquired immunodeficiency? S Afr Med J. 1988 Dec 17;74(12):610–614. [PubMed] [Google Scholar]
  4. Biberfeld P., Petrén A. L., Eklund A., Lindemalm C., Barkhem T., Ekman M., Ablashi D., Salahuddin Z. Human herpesvirus-6 (HHV-6, HBLV) in sarcoidosis and lymphoproliferative disorders. J Virol Methods. 1988 Sep;21(1-4):49–59. doi: 10.1016/0166-0934(88)90051-1. [DOI] [PubMed] [Google Scholar]
  5. Biron C. A., Byron K. S., Sullivan J. L. Severe herpesvirus infections in an adolescent without natural killer cells. N Engl J Med. 1989 Jun 29;320(26):1731–1735. doi: 10.1056/NEJM198906293202605. [DOI] [PubMed] [Google Scholar]
  6. Blanchard D. K., Friedman H., Stewart W. E., 2nd, Klein T. W., Djeu J. Y. Role of gamma interferon in induction of natural killer activity by Legionella pneumophila in vitro and in an experimental murine infection model. Infect Immun. 1988 May;56(5):1187–1193. doi: 10.1128/iai.56.5.1187-1193.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carney W. P., Hirsch M. S. Mechanisms of immunosuppression in cytomegalovirus mononucleosis. II. Virus-monocyte interactions. J Infect Dis. 1981 Jul;144(1):47–54. doi: 10.1093/infdis/144.1.47. [DOI] [PubMed] [Google Scholar]
  8. Drew W. L., Mintz L., Hoo R., Finley T. N. Growth of herpes simplex and cytomegalovirus in cultured human alveolar macrophages. Am Rev Respir Dis. 1979 Feb;119(2):287–291. doi: 10.1164/arrd.1979.119.2.287. [DOI] [PubMed] [Google Scholar]
  9. Frenkel N., Schirmer E. C., Katsafanas G., June C. H. T-cell activation is required for efficient replication of human herpesvirus 6. J Virol. 1990 Sep;64(9):4598–4602. doi: 10.1128/jvi.64.9.4598-4602.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Frenkel N., Schirmer E. C., Wyatt L. S., Katsafanas G., Roffman E., Danovich R. M., June C. H. Isolation of a new herpesvirus from human CD4+ T cells. Proc Natl Acad Sci U S A. 1990 Jan;87(2):748–752. doi: 10.1073/pnas.87.2.748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Griffiths P. D., Grundy J. E. The status of CMV as a human pathogen. Epidemiol Infect. 1988 Feb;100(1):1–15. doi: 10.1017/s095026880006550x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Krueger G. R., Koch B., Ablashi D. V. Persistent fatigue and depression in patient with antibody to human B-lymphotropic virus. Lancet. 1987 Jul 4;2(8549):36–36. doi: 10.1016/s0140-6736(87)93064-9. [DOI] [PubMed] [Google Scholar]
  13. Lawrence G. L., Chee M., Craxton M. A., Gompels U. A., Honess R. W., Barrell B. G. Human herpesvirus 6 is closely related to human cytomegalovirus. J Virol. 1990 Jan;64(1):287–299. doi: 10.1128/jvi.64.1.287-299.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Levy J. A., Ferro F., Greenspan D., Lennette E. T. Frequent isolation of HHV-6 from saliva and high seroprevalence of the virus in the population. Lancet. 1990 May 5;335(8697):1047–1050. doi: 10.1016/0140-6736(90)92628-u. [DOI] [PubMed] [Google Scholar]
  15. Lusso P., Markham P. D., Tschachler E., di Marzo Veronese F., Salahuddin S. Z., Ablashi D. V., Pahwa S., Krohn K., Gallo R. C. In vitro cellular tropism of human B-lymphotropic virus (human herpesvirus-6). J Exp Med. 1988 May 1;167(5):1659–1670. doi: 10.1084/jem.167.5.1659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McVoy M. A., Adler S. P. Immunologic evidence for frequent age-related cytomegalovirus reactivation in seropositive immunocompetent individuals. J Infect Dis. 1989 Jul;160(1):1–10. doi: 10.1093/infdis/160.1.1. [DOI] [PubMed] [Google Scholar]
  17. Meyer R. D. Legionella infections: a review of five years of research. Rev Infect Dis. 1983 Mar-Apr;5(2):258–278. doi: 10.1093/clinids/5.2.258. [DOI] [PubMed] [Google Scholar]
  18. Morris D. J., Littler E., Arrand J. R., Jordan D., Mallick N. P., Johnson R. W. Human herpesvirus 6 infection in renal-transplant recipients. N Engl J Med. 1989 Jun 8;320(23):1560–1561. [PubMed] [Google Scholar]
  19. Nash T. W., Libby D. M., Horwitz M. A. IFN-gamma-activated human alveolar macrophages inhibit the intracellular multiplication of Legionella pneumophila. J Immunol. 1988 Jun 1;140(11):3978–3981. [PubMed] [Google Scholar]
  20. Niederman J. C., Liu C. R., Kaplan M. H., Brown N. A. Clinical and serological features of human herpesvirus-6 infection in three adults. Lancet. 1988 Oct 8;2(8615):817–819. doi: 10.1016/s0140-6736(88)92783-3. [DOI] [PubMed] [Google Scholar]
  21. Okuno T., Higashi K., Shiraki K., Yamanishi K., Takahashi M., Kokado Y., Ishibashi M., Takahara S., Sonoda T., Tanaka K. Human herpesvirus 6 infection in renal transplantation. Transplantation. 1990 Mar;49(3):519–522. doi: 10.1097/00007890-199003000-00009. [DOI] [PubMed] [Google Scholar]
  22. Pietroboni G. R., Harnett G. B., Bucens M. R., Honess R. W. Isolation of human herpesvirus 6 from saliva. Lancet. 1988 May 7;1(8593):1059–1059. doi: 10.1016/s0140-6736(88)91884-3. [DOI] [PubMed] [Google Scholar]
  23. Salahuddin S. Z., Ablashi D. V., Markham P. D., Josephs S. F., Sturzenegger S., Kaplan M., Halligan G., Biberfeld P., Wong-Staal F., Kramarsky B. Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science. 1986 Oct 31;234(4776):596–601. doi: 10.1126/science.2876520. [DOI] [PubMed] [Google Scholar]
  24. Takahashi K., Sonoda S., Higashi K., Kondo T., Takahashi H., Takahashi M., Yamanishi K. Predominant CD4 T-lymphocyte tropism of human herpesvirus 6-related virus. J Virol. 1989 Jul;63(7):3161–3163. doi: 10.1128/jvi.63.7.3161-3163.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tanaka J., Ogura T., Kamiya S., Sato H., Yoshie T., Ogura H., Hatano M. Enhanced replication of human cytomegalovirus in human fibroblasts treated with dexamethasone. J Gen Virol. 1984 Oct;65(Pt 10):1759–1767. doi: 10.1099/0022-1317-65-10-1759. [DOI] [PubMed] [Google Scholar]
  26. Toorkey C. B., Carrigan D. R. Immunohistochemical detection of an immediate early antigen of human cytomegalovirus in normal tissues. J Infect Dis. 1989 Nov;160(5):741–751. doi: 10.1093/infdis/160.5.741. [DOI] [PubMed] [Google Scholar]
  27. Webel M. L., Ritts R. E., Jr, Taswell H. F., Danadio J. V., Jr, Woods J. E. Cellular immunity after intravenous administration of methylprednisolone. J Lab Clin Med. 1974 Mar;83(3):383–392. [PubMed] [Google Scholar]
  28. West P. G., Aldrich B., Hartwig R., Haller G. J. Increased detection of herpes simplex virus in MRC-5 cells treated with dimethyl sulfoxide and dexamethasone. J Clin Microbiol. 1989 Apr;27(4):770–772. doi: 10.1128/jcm.27.4.770-772.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Winn W. C., Jr, Myerowitz R. L. The pathology of the Legionella pneumonias. A review of 74 cases and the literature. Hum Pathol. 1981 May;12(5):401–422. doi: 10.1016/s0046-8177(81)80021-4. [DOI] [PubMed] [Google Scholar]
  30. Yamanishi K., Okuno T., Shiraki K., Takahashi M., Kondo T., Asano Y., Kurata T. Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet. 1988 May 14;1(8594):1065–1067. doi: 10.1016/s0140-6736(88)91893-4. [DOI] [PubMed] [Google Scholar]

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